Life cycle ♦ The organism is transmitted by the bite of several species of blood-feeding sand flies (Phlebotomus) which carries the promastigote in the anterior gut and pharynx. Promastigote of Leishmania sp Life cycle
Promastigote gains access to mononuclear phagocytes where it transform into and divides until the infected cell ruptures. The released organisms infect other cells. ♦ Promastigote gains access to mononuclear phagocytes where it transform into amastogotes and divides until the infected cell ruptures. The released organisms infect other cells. Promastigote gains access to mononuclear phagocytes where it transform into and divides until the infected cell ruptures. The released organisms infect other cells. ♦ Promastigote gains access to mononuclear phagocytes where it transform into amastigotes and divides until the infected cell ruptures. The released organisms infect other cells.
Life cycle ♦ The sandfly acquires the organisms during the blood meal, the amastigotes transform into flagellate promastigotes and multiply in the gut until the anterior gut and pharynx are packed. Dogs and rodents are common reservoirs. *Phlebotomus sendfly is the VECTOR of Leishmania
Clinical Disease Visceral –Fatal (90% untreated) –Liver –Spleen –Bone marrow Cutaneous Generally Self- healing –Skin Mucous membranes Muco cutanous mucosal involvement may occur if a skin lesion near the mouth or nose is not treated
Life cycle of Leishmania
Initial Infection of Leishmania Similar in all species Inoculation of promastigotes Inflammation & chemotaxis Receptor mediated phagocytosis Promastigote Amasitgote Transformation
Main Points of Life Cycle ♦ Host: man and sandfly ♦ No sexual development in the host ♦ Residing site: macrophage ♦ Infective stage: promastigote ♦ Infective route: inoculation of sandfly ♦ Reservoir host: dog ♦ Infection could also via transfusion
Cutaineous Leishmaniasis Clinical manifestation ♦ Most common form ♦ Characterized by one or more sores, papules or nodules on the skin ♦ Sores can change in size and appearance over time ♦ Often described as looking somewhat like a volcano with a raised edge and central crater
Cutaineous Leishmaniasis Clinical manifestation ♦ Sores are usually painless but can become painful if secondarily infected ♦ Swollen lymph nodes may be present near the sores (under the arm if the sores are on the arm or hand…)
Cutaineous Leishmaniasis Clinical manifestation ♦ Most sores develop within a few weeks of the sandfly bite, however they can appear up to months later ♦ Skin sores of cutaneous leishmaniasis can heal on their own, but this can take months or even years
Cutaineous Leishmaniasis Clinical manifestation ♦ Sores can leave significant scars and be disfiguring if they occur on the face ♦ If infection is from L. tropica it can spread to contiguous mucous membranes (upper lip to nose)
Cutaineous leishmaniasis Causative organism L. tropica L. major L. aethiopica L. mexicana Location Mediterranean basin, Afghanistan Middle East, W. and N. Africa, Kenya Ethiopia Central America and Amazon.
Cutaineous leishmaniasis of the face.
Visceral Leishmaniasis KALA-AZAR Most severe form of the disease, may be fatal if left untreated Usually associated with fever, weight loss, and an enlarged spleen and liver Anemia (low RBC), leukopenia (low WBC), and thrombocytopenia (low platelets) are common Lymphadenopathy may be present
Visceral Leishmaniasis Causative organism L.donovanii L.d.donovani L.d.infantum L.d chagasi Location China, India, Iran Sudan, Kenya, Ethiopia Mediterranean region Brazil, Colombia, Venezuela, Argentina
Visceral Leishmaniasis in Desert Storm The following symptoms were found in eight visceral leishmaniasis patients returning from Desert Storm Fevers: 6 of 8 Weight loss: 2 of 8 Nausea, vomiting, low-grade watery diarrhea: 2 of 8 Lymphadenopathy: 2 of 8 Hepatosplenomegly: 2 of 8 Anemia: 3 of 8 Leukopenia or thrombocytopenia: 0 of 8 Elevated liver enzymes: 6 of 8 No symptoms: 1 of 8 Magill et al, NEJM 1993:328(19)
Visceral Leishmaniasis ♦ Symptoms usually occur months after sandfly bite ♦ Because symptoms are non-specific and often start after redeployment there is usually a delay in diagnosis ♦ Visceral leishmaniasis should be considered in any CHRONIC FEVER patient returning from an endemic area.
♦ Profile view of a teenage boy suffering from visceral leishmaniasis. The boy exhibits splenomegaly, distended abdomen and severe muscle wasting.
♦ A 12-year-old boy suffering from visceral leishmaniasis. The boy exhibits splenomegaly and severe muscle wasting.
♦ Jaundiced hands of a visceral leishmaniasis patient.
♦ Enlarged spleen and liver in an autopsy of an infant dying of visceral leishmaniasis.
♦ Occurs with Leishmania species from Central and South America ♦ Very rarely associated with L. tropica which is found in the Middle East - This type occurs if a cutaneous lesion on the face spreads to involve the nose or mouth - This rare mucosal involvement may occur if a skin lesion near the mouth or nose is not treated
Muco cutaineous Leishmaniasis Causative organism Location L. braziliensis complex Brazil, Peru, Ecuador, Columbia, Venezuela
Control ♦ Vector control ♦ Reservoir control ♦ Treatment of active cases ♦ Vaccination
Diagnosis ♦ Clinical signs & symptoms ♦ Hypergammaglobulinemi ♦ ELISA/Formol gel ♦ Bone marrow biopsy ♦ Spleen or liver biopsy ♦ Culture & Histology
Diagnosis: Cutaneous Leishmaniasis Patients with any of the following findings should be referred early to avoid long term complications: Big lesions (greater than an inch in size) Many lesions (3 or more) Sores on the face Sores on the hands and feet Sores over joints
Treatment Cutaneous and Mucocutaneous Antimony (Pentostam ®, Sodium stibogluconate) is the drug of choice 20 days of intravenous therapy Fluconazole may decrease healing time in L. major infection Biopsy and culture to determine species is required Six weeks of therapy is needed
Treatment Visceral Leishmaniasis ♦ Liposomal amphotericin-B (AmBisome®) is the drug of choice 3 mg/kg per day on days 1-5, day 14 and day 21 ♦ Pentostam ® is an alternative therapy 28 days of therapy is required ♦ Although AmBisome ® is widely available,
J Med Entomol May;36(3): Sandflies (Diptera: Psychodidae) associated with epidemic cutaneous leishmaniasis in Sanliurfa, Turkey. Alptekin D, Kasap M, Luleyap U, Kasap H, Aksoy S, Wilson ML.Alptekin DKasap MLuleyap UKasap HAksoy SWilson ML Department of Medical Biology, Faculty of Medicine, Cukurova University, Balcali, Adana, Turkey. As part of a project to study the possible impact of environmental change on health in southeastern Turkey, we evaluated sandfly species diversity, abundance, and habitat associations in an urban area where cutaneous leishmaniasis was undergoing epidemic re-emergence. Houses and caves in and around the city of Sanliurfa, Turkey, were sampled using mechanical aspirators, sticky papers, and CDC light traps. Of 1,649 sandflies captured, including 6 Phlebotomus and 1 Sergentomyia species, nearly all were P. papatasi (Scopoli) (967) or P. sergenti Parrot (674). Sandflies were active during June-September (hot dry season), but not during January (cool rainy season). Resting phlebotomines were abundant inside houses. Houses sampled in 3 neighborhoods with a high cutaneous leishmaniasis incidence (9-65 cases per 1,000 population) had > 10 times more flies than at a comparison site where few cases (0.2 per 1,000) have been reported. Results indicated that P. sergenti or P. papatasi were the probable vectors of cutaneous leishmaniasis during this outbreak and that control of these sandflies may eliminate transmission.
BLOOD AND TISSUE PROTOZOONS TOXOPLASMA
Agent:Toxoplasma gondii Agent: Toxoplasma gondii TaxonomyTaxonomy: Phylum Apicomplexa DistributionDistribution: Worldwide Definitive HostDefinitive Host: Any member of the Felidae Intermed. HostsIntermed. Hosts: Any warm blooded animal Invertebrates:Invertebrates: Coprophagous (“feces- eating”) InsectsInsects can be transport hosts Toxoplasmosis
Human toxoplasmosis Inapparent or mild flu-like illness (most cases) Fetal death and mental retardation, blindness, Epilepsy…. May not manifest for years ~ congenital infections/year Ocular toxoplasmosis Severe encephalitis in İmmunocompromised persons.
Life Stages of Toxoplasma Tachyzoites = proliferative form in blood or CSF,acute or recurrent Bradyzoites = lifelong “tissue cysts”, any host Oocysts = (with sporozoites) shed in feces after completion of sexual phase in feline gut epithelium. Infectious after 48 hours or more environmental incubation. Oocysts Survive months to years despite freezing, heat, dehydration Thousands-to-millions shed per cat Oocysts are shed from cats for 1-2 weeks only. Only ~1% of cats are shedding oocysts at a given time
Life Cycle Toxoplasma
The only known definitive hosts for Toxoplasma gondii are members of family Felidae (domestic cats and their relatives). 1 1-Unsporulated oocysts are shed in the cat’s feces 2 2- Although oocysts are usually only shed for 1-2 weeks, large numbers may be shed. Oocysts take 1-5 days to sporulate in the environment and become infective. Intermediate hosts in nature (including birds and rodents) become infected after ingesting soil, water or plant material contaminated with oocysts Oocysts transform into tachyzoites shortly after ingestion. These tachyzoites localize in neural and muscle tissue and develop into tissue cyst bradyzoites Cats become infected after consuming intermediate hosts harboring tissue cysts. Cats may also become infected directly by ingestion of sporulated oocysts. Animals bred for human consumption and wild game may also become infected with tissue cysts after ingestion of sporulated oocysts in the environment. 5 5-Humans can become infected by any of several routes:
Toxoplasma gondii Tachyzoites bradyzoitesTachyzoites are the motile, asexually reproducing form of the parasite. Unlike the bradyzoites, the free tachyzoites are usually efficiently cleared by the host's immune response, although some manage to infect cells and form bradyzoites, thus maintaining the infection.
Routes of Transmission of Toxoplasma Foodborne (third leading cause of all types) Waterborne Contaminated soil Transplacental Organ transplants Blood transfusion Laboratory accidents
Life Stages of T.gondii in Cats Types A-E are sexual phases, all completed in feline gut epithelium. Prepatent periods: Tissue Cysts: 3-10 days Oocysts: > 18 days Tachyzoites: > 13 days
T. Gondii Oocysts Unsporulated TransmissionElectron Microscopy - showing sporocysts each containing sporozoites
♦ Accidental ingestion of contaminated cat feces. For example,accidental touching of hands to mouth after gardening, cleaning a cat’s litter box, or touching anything that has come into contactwith cat feces. ♦ Ingestion of raw or partly cooked meat, especially pork, lamb, or venison, or by touching hands to mouth after handling undercooked meat.
Sources of T. gondii exposure ♦ Contamination of knives, utensils, cutting boards and other foods that have had contact with raw meat. ♦ Drinking water contaminated with Toxoplasma. ♦ Although extremely rare, by receiving an infected organ transplant.
Human Risks from Cat Contact ♦ Oocysts sporulate in 48 hours+ at room temperatures. ♦ Most cats do not leave feces on their fur for two days, so it is unlikely that humans become infected from direct contact with cats themselves. ♦ Because cats usually exhibit no signs of illness while passing oocysts, it is difficult to determine when a particular cat's feces may be infectious to people or other mammals. ♦ Most adult cats will not pass oocysts ever again after recovering from an initial exposure to Toxoplasma.
Congenital Toxoplasmosis ♦ Manifestations of congenital toxoplasmosis may not become apparent until the second or third decade of life. ♦ Serologic tests are used to diagnose acute infection in pregnant women, but false-positive tests occur frequently, therefore, serologic diagnosis must be confirmed at a reference laboratory before treatment with potentially toxic drugs should be considered. Infant girl with T.gondii hydrocephalus
Congenital T. gondii Infections Many false positives via some kits (8 brands) Send to reference lab for confirmation before treatment PCR of amniotic fluid useful for test confirmation/exclusion Pyrimethamine & sulfonamide for positive PCR-AF tests Spiramycin for negative PCR-AF tests
Toxoplasma encephalitis The most frequent cause of focal CNS infections in AIDS patients
Toxoplasma gondii and Schizophrenia E. Fuller Torrey* and Robert H. Yolken† *Stanley Medical Research Institute, Bethesda, Maryland, USA; (2003) Recent epidemiologic studies indicate that infectious agents may contributeto some cases of schizophrenia. In animals, infection with Toxoplasmagondii can alter behavior and neurotransmitter function. In humans, acuteinfection with T. gondii can produce psychotic symptoms similar to thosedisplayed by persons with schizophrenia. Since 1953, a total of 19 studies of T. gondii antibodies in persons withschizophrenia and other severe psychiatric disorders and in controls havebeen reported; 18 reported a higher percentage of antibodies in theaffected persons; in 11 studies the difference was statistically significant. Two other studies found that exposure to cats in childhood was a risk factor for the development of schizophrenia.
Toxoplasmosis Treatment of toxoplasmosisTreatment of toxoplasmosis in immunocompetent patients is usually unnecessary. In immunocompromised patients, the recommended treatment is a combination of pyrimethamine given at mg daily and trisulfapyrimidines given at 2-6 g daily, both for a month. This drug combination inhibits dihydrofolate reductase in T. gondii, preventing synthesis of DNA and protein.
Toxoplasmosis infected pregnant womenIn acutely infected pregnant women, the recommended treatment includes spiramycin if the fetus has not yet acquired toxoplasmosis. SpiramycinSpiramycin is an antibiotic that localizes to the placenta and has been shown to reduce placental infection by 60%. It does have some teratogenic effects, which must be weighed against the risk of congenital infection. If the fetus is infected, the aforementioned drug combination is administered instead of spiramycin.